Electon microscopic observations were made on liver biopsy specimens from nine infants and children diagnosed as having Reye's syndrome by clinical, laboratory, and light microscopic criteria. In addition to excessive fat content, mitochondrial abnormalities were the most frequent abnormal finding in the liver. However, no correlation could be established between the severity of mitochondrial changes and clinical or biochemical data, and two patients with low levels of the first two urea cycle enzymes showed only mild mitochondrial abnormalities. Nonspecific or artifactual factors have been suggested to explain the mitochondrial changes. However, the data of this study suggest that most of the reported mitochondrial abnormalities are not artifacts, and that they can be helpful in the ultrastructural diagnosis of Reye's syndrome.